Modulation nutritionnelle du métabolisme énergétique par l’oligofructose : caractérisation des mécanismes moléculaires dans un modèle murin
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- Prebiotic consumption is widely recognized for its beneficial effects on metabolic health through gut microbiota modulation, representing a promising nutritional strategy for preventing or improving metabolic diseases. We have previously demonstrated that oligofructose (FOS) supplementation counteracts diet-induced obesity, accompanied by significant intestinal remodeling. However, the molecular mechanisms linking these intestinal adaptations to systemic metabolic improvements remain poorly understood, and the effects of FOS supplementation under a control diet are not well characterized. In this study, we evaluated the impact of FOS on the global energy metabolism of nine-week-old male mice fed either a high-fat diet (HFD) or a normal control diet (ND). Indirect calorimetry was used to precisely assess the prebiotic's effects on energy expenditure and substrate utilization. After a seven-week intervention, FOS significantly reduced fat mass gain and increased lean mass in mice on the ND. In the HFD context, FOS improved glucose homeostasis, as evidenced by enhanced glucose tolerance and a reduction in the insulin resistance index. Furthermore, a marked decrease in ectopic intrahepatic lipid droplet accumulation was observed under the HFD. Calorimetric analysis revealed a state of systemic hypermetabolism: FOS significantly increased total energy expenditure, regardless of the dietary regimen. In obese mice, FOS restored metabolic flexibility, as shown by an elevated respiratory quotient reflecting an improved capacity for carbohydrate oxidation. These systemic effects correlated with major intestinal adaptations, including massive cecal hypertrophy and proglucagon overexpression in the colon and cecum, suggesting increased secretion of the incretin peptides GLP-1 and GLP-2. Finally, the study highlights a "bioenergetic paradox": while FOS induces browning of subcutaneous white adipose tissue under the standard diet, this transcriptional effect is absent under HFD. Nonetheless, FOS prevents the whitening of brown adipose tissue. In conclusion, oligofructose acts as a potent metabolic modulator capable of reprogramming energy homeostasis via the gut-organ axis, offering concrete therapeutic perspectives for obesity management.